Important Books & Reports

Glyphosate/Roundup, falsely claimed by Monsanto to be safe and harmless, has become the world’s most widely and pervasively used herbicide; it has brought rising tides of birth defects, cancers, fatal kidney disease, sterility, and dozens of other illnesses - more

Ban GMOs Now - Dr. Mae-Wan Ho and Dr. Eva Sirinathsinghji

Health & environmental hazards
especially in the light of the new genetics - more

Living Rainbow H2O - Dr. Mae-Wan Ho

A unique synthesis of the latest findings in the quantum physics and chemistry of water that tells you why water is the “means, medium, and message of life” - more

The Rainbow and the Worm - the Physics of Organisms - Dr. Mae-Wan Ho

“Probably the Most Important Book for the Coming Scientific Revolution” - more

Synthetic Life? Not By a Long Shot

Dr. Mae-Wan Ho exposes the hype that scientists have created life but is cautiously optimistic provided no patents are granted on life, synthetic or otherwise

The hype

Scientists have created life in the
test-tube? The popular media appeared to have gone into overdrive on the latest
episode in the long-running saga of ‘synthetic biology’. The same happened when
the human genome sequence was announced ten years ago as the “book of life”,
though it told us absolutely nothing on how to make life, let alone a human
being.

The media are
only slightly exaggerating what the scientists themselves are claiming. The
title of the article published online 20 May 2010 in Science Express is
[1] “Creation [emphasis added] of a bacterial cell controlled by a
chemically synthesized genome.” It had 24 co-authors including team leader J.
Craig Venter from the J. Craig Venter Institute based in Rockville, Maryland, and San Diego, California, in the United States. Venter is the maverick who famously
came up from behind to an ‘equal finish’ with the public consortium in the race
to sequence the entire human genome. And he is grabbing the headlines again
with the latest stunt.

The hopes and fears

So is this the genesis of the brave new
world of synthetic life-forms owned and controlled by unaccountable corporations
hungry for power and profit that would make our worst nightmares come true? Or is
it the greatest boon to mankind that will solve all the problems that human
folly has created, beginning with cleaning up the gigantic and still growing
oil spill in the Gulf of Mexico, and going on to the energy crisis and climate
change?

Mark Bedau, a philosopher at
Reed College in Portland, Oregon, and editor of the journal Artificial Life,
calls it “a defining moment in the history of biology and biotechnology”, while
yeast biologist Jef Boeke at John Hopkins University School of Medicine in Baltimore, Maryland, says it is “an important technical milestone in the new field of
synthetic genomics” [2].

Professor
Julian Savulescu from the Oxford Uehiro Centre for Practical Ethics at Oxford University
tells the BBC [3] that the potential of this science is “in the far future, but
real and significant”, though “the risks are also unparalleled. We need new standards
of safety evaluation for this kind of radical research and protections from
military or terrorist misuse and abuse.These could be used in the future
to make the most powerful bioweapons imaginable. The challenge is to eat the
fruit without the worm.”

Paul Rabinow, an anthropologist
at the University of California Berkeley, says the experiment will “reconfigure
the ethical imagination” [2]. Kenneth Oye, a social scientist at the Massachusett s institute of Technology in Cambridge sums up: “we are shooting in the dark
as to what the long-term benefits and long-term risks will be.”

The science

The tiny genome of the bacteriophage fX174 (5 386
bases) was sequenced in 1977. It took another 18 years before Venter and
colleagues sequenced the first genome of a self-replicating bacterium, Haemophilus
influenzae (1 830 137 bp). Since then, the
speed of sequencing genomes has increased exponentially, as has the ability to
digitize genomic information [1].

Venter and his
team got the idea of building a minimal cell that contains only essential genes
in 1995, when they sequenced the 580 kbp genome from Mycoplasma genitalium,
a bacterium with the smallest number of genes of any known self-replicating
organism.

Through a long
series of experiments that involved knocking out the genes one by one, they
found that 100 of the 485 protein-coding genes are surplus to requirement.

Next, they
developed a strategy for assembling genomes of viruses that are large DNA
molecules, though much smaller than those of bacteria, as a stepping stone to making
the synthetic genome of M. genitalium. That was accomplished in four
stages, first by joining up DNA pieces averaging about 6 kb in size, then
proceeding on to larger sizes, both in the test tube and in cells of the yeast Saccharomyces
cerevisiae. The entire synthetic genome was stably replicated as a special
yeast extrachromosomal plasmid.

A major bottleneck
to progress was the slow growth rate of M. genitalium. So the team
switched to two faster growing species M. mycoides subspecies capri as
genome donor and M. cacpriocolum subspecies capricolum as recipient.

The team also had to develop a
method for cloning entire bacterial chromosomes in yeast as plasmids with
centromeres. A centromere is a special part of the chromosome responsible for
getting each of the replicated chromosome to a daughter cell during cell
division, so the chromosome could be stably propagated..

Their initial
attempts to extract the M. mycoides genome from yeast and transplant it
into M capriocolum failed. The native M. mycoides genome had
extra signals to protect it from being broken down by DNA-cutting enzymes
(restriction enzymes); and the same enzymes are present in the donor and
acceptor species. The signals consist of specific DNA bases that are methylated
(methyl group added), so restriction enzymes cannot recognize the cutting sites.
The chromosomes grown in yeast cells are unfortunately non-methylated. To solve
that problem, the team methylated the donor DNA with purified methylases, enzymes
that do the job, or simply with crude extracts of M. mycoides or M.
capricolum containing the methylases.

The team started
building the synthetic chromosome by “going DNA shopping” [2]. They bought more
than a thousand 1 080-base sequences that covered the entire M. mycoides
genome to make it easier to assemble the pieces in correct order, as the ends
of each sequence had 80 bases that overlapped with its neighbours. In order to
mark it as a synthetic genome, four of the pieces contained sequences that in
code spelt out an e-mail address, the names of many of the people involved in
the project, and a few famous quotations besides.

They used yeast
to assemble the pieces in stages, first splicing 10 starting pieces together to
make 10 000-base sequences, then 100 000-base sequences, and finally the
complete 1 080 000-base genome [1].

But when they
tried to put the synthetic genome into M. capricolum, nothing happened.
It took them three months to track down a single-base error responsible for the
glitch. A single bp deletion had frame-shifted the entire polypeptide chain of
an enzyme essential for DNA replication. They corrected the error, and some
months later, the breakthrough arrived.

A tiny blue
colony was growing on the agar plate, the blue colour an indicator that a cell
had taken up the synthetic genome and was multiplying successfully with it. To
confirm, they sequenced the DNA in the colony, and found it was indeed the
synthetic genome complete with the “water mark” of extra sequences inserted.
The microbes were making proteins characteristic of the donor M. mycoides
rather than M. capricolum, as checked by two-dimensional gel
electrophoresis. They have genetically modified the bacterium entirely
by giving it the genome of another species.

No life was created

Clearly the scientists have not
created life or the bacterial cell. There is a yawning chasm in the physics and
chemistry of the living state [4] (The
Rainbow and the Worm, The Physics of Organisms, ISIS publication) that the
team hasn’t even begun to address, let alone bridge. They did not create the
genome that was used to transform the bacteria cell, only copied it from
another species of the genus, adding a “water mark” for identification, and no
doubt, for staking their claim to the synthetic genome. This synthetic genome
was not even made from scratch, but cobbled together from pieces found in a
catalogue, and then ‘transplanted’ into cells of the recipient bacterium species
(a close relative of the donor) using an antibiotic to select for cells that
have accepted the artificial chromosome and allow them to grow. The procedure
is similar to the nuclear transplant experiment that made Dolly the cloned sheep
in the 1990s and other animals since.

Anthony Forster,
a molecular biologist at Vanderbilt University in Nashville, Tennessee, lauds the
“pretty amazing accomplishment”, but is among those stressing that the work did
not really create life because the genome was put into an existing cell [2].

In many ways, synthetic
biology is a linear progression from genetic engineering, only much more
extensive and sophisticated, thanks to quantum leaps in DNA sequencing and
synthesis techniques, and exponential growth in information technology within
the past decade.

No patents on life, artificial or
otherwise

No one should underestimate the potential
risks of synthetic biology. Already, the disastrous health and environmental
impacts of genetically modified organisms are coming to light all over the
world (see my Foreword to GM Food Angel or
Devil [5] for a succinct summary). Nevertheless, there are also potential
benefits to synthetic biology.

The approach can
open the door to much more precise design of ‘synthetic’ organisms, which, if successful,
are just greatly improved genetically modified microorganisms that could help clean
up oil spills and make hydrogen from water, for example.

The techniques could
also contribute to basic scientific understanding of how the fluid genome works
(see [6] Living with the
Fluid Genome, ISIS publication) and solve the age-old conundrum of
nuclear-cytoplasmic interactions in heredity and development (see [7-9] Beyond neo-Darwinism: an Epigenetic Approach to Evolution,
Environment and Heredity in Development and
Evolution, and Development
and Evolution Revisited ISIS Scientific publications).

These and other
potential benefits of synthetic biology can only be realised if it is
kept in the public domain, and no patents are granted for putative “synthetic
organisms” that should remain strictly contained and confined in the laboratory
unless and until proven safe for health and the environment.

Venter says his
institute has already applied for several patents on the work [2]. The technology
watchdog ETC based in Ottawa has argued these could result in a monopoly on
synthetic biology. The monopoly on genes and genetic modification has already
proven disastrous for scientific research and the public good [10] (Corporate
Monopoly of Science, SiS 42). The controversial breast cancer gene
patents have been challenged by a large coalition of learned societies,
scientists, not-for-profit organisations and individual patients, and declared
invalid by a judge in a New York City district court at the end of March 2010
[11].

What are the ethical
dimensions? I don’t see any ethical dimensions different from those of cloned or
genetically modified organisms (see [12] Human Farm Incorporated and
other articles in the series, SiS 13/14, and [13] Transgenic Animals for Food Not
Proven Safe, SiS 41). Synthetic organisms have the same potential of
abuse and misuse, and need to be thoroughly scrutinised and openly discussed
without the restrictions of patents that grant ownership to life, synthetic or
otherwise.

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There are 2 comments on this article so far. Add your comment above.

Rory Short Comment left 25th May 2010 14:02:18I agree the only way to progress in this matter is 'without the restrictions of patents that grant ownership to life, synthetic or otherwise'.
Granting patents on the essentials of life is illogical. It is 'the whole' authorising parts of itself, the patent holders,to have exclusive ownership of parts of itself. This simply does not make sense. It is an attempt to deny the very fact that life, of which we each are an individual expression, belongs to all of us not to any particular subset of us.

tony villar Comment left 25th May 2010 14:02:07dr.Ho.
pls keep up the good work.